Project Summary/Abstract This research will investigate central nervous system mechanisms underlying exercise as a strategy to promote resilience to social stressors, and is specifically designed to provide a training environment for undergraduate students. Exposure to social stressors significantly reduces quality of life, contributing to emotion-related disorders such as depression, physiological disorders such as heart disease, and premature mortality. However, our understanding of the mechanisms underlying social stressors and potential sex differences in stress vulnerability and resilience is limited. Therefore, strategies designed to promote resilience to social stressors in both sexes will improve public health. The present project will use a rodent model ? the socially monogamous prairie vole ? to investigate behavioral, autonomic, and endocrine reactivity to long-term social isolation (Specific Aim 1), and potential molecular and neuropeptide mechanisms that underlie exercise as a prevention strategy against social isolation (Specific Aim 2). The prairie vole is a valuable model system for studying responsiveness to social experiences and neurobiological mechanisms underlying stress-related disorders. This species displays several unique social behaviors that mimic those of humans, including living in extended families, forming enduring social bonds, and displaying behavioral, physiological, and neural changes as a function of social stressors. Voluntary exercise may serve a protective role against some depression-relevant behaviors and endocrine responses in socially isolated prairie voles; however the mechanisms underlying these benefits are not clear. Therefore, using male and female prairie voles, Specific Aim 1 will employ continuous recording of autonomic variables (e.g., heart rate, heart rate variability), repeated corticosterone measurements, and behavioral tests of depression and stress reactivity to test the hypothesis that exercise is an effective strategy to promote resilience to behavioral and physiological effects of social isolation in a sex-specific and activity level-specific manner. Specific Aim 2 will employ measures of central delta-FosB and neuropeptide immunoreactivity, to investigate the hypothesis that long-term alterations in cortical, limbic, and autonomic brain regions underlie the protective effects of exercise. We hypothesize that exercise will, in a sex-specific manner: (a) prevent long-term autonomic and endocrine consequences of isolation; (b) improve behavioral and physiological reactivity to stressors; and (c) improve neural activity in regions of the brain relevant to social behavior, stress, and autonomic and endocrine processes including the medial prefrontal cortex, hypothalamus, hippocampus, amygdala, bed nucleus of the stria terminalis, medullary structures, and dorsal vagal complex. This research proposes novel mechanisms through which exercise can protect against behavioral and physiological consequences of social isolation. The findings from this project will facilitate realistic strategies to promote resilience to social stress in both women and men.